For the industrial manufacturing of pharmaceutical capsules gelatine is most preferred for its gelling, film forming and surface active properties. The manufacture of hard gelatin capsules by dip moulding process exploits fully its gelling and film forming abilities. Such capsules are manufactured by dipping mould pins into a hot solution of gelatin, removing the pins from the gelatin solution, allowing the gelatin solution attached on pins to set by cooling, drying and stripping the so-formed shells from the pins. The setting of the solution on the mould pins after dipping is the critical step to obtain an uniform thickness of the capsule shell.
A main limitation of the use of hard gelatine capsules results from an exchange of moisture between capsules and fills. Gelatine naturally has hygroscopic properties and hard gelatine capsules generally contain about 10 to 16% by weight of water. This water content is a function of the relative humidity (RH) of the surroundings. When capsules are filled and stored in a vapour tight container, the moisture will redistribute between the various components until an uniform relative humidity is attained in the vapor phase of capsule shell, fill and surrounding.
A further disadvantage of the gelatin film and an unwanted limitation of its use is its high water vapour permeability, which results in a high rate of water vapour transport through the gelatine shell of capsules with a hygroscopic fill or of capsules stored in a humid environment. Results of experimental tests show that at 22° C. by a difference of 50% in the RH between both sides of a 100 μm gelatine film during a period of 24 hours an amount of twice the gelatin film weight of water vapour is permeated through the film. Consequently, when capsules exposed to an open environment, the fill will take up moisture from the environment by permeation through the capsule shell until equilibrium is achieved.
Moisture take-up of the fill of a capsule by moisture exchange with or permeation through the capsule shell may adversely affect the properties of the fill: powder fills may agglomerate or, more seriously, fills may undergo chemical degradation e.g. by hydrolysis. Generally pharmaceutical gelatin capsules therefore are to be stored a dry environment.
The affinity of capsules and their fills and the moisture exchange between capsules and fills can be determined by the sorption-desorption isotherms for the materials of capsules and fills. For gelatine this is well described in the literature, e.g. in K. Ito & al., Chem. Pharm. Bull. 17 (3) 1969, 1134–37. M. J. Kontny & al., Int. J. Pharm. 54, 1989, 79–85 describe a mathematical model to predict the final relative water vapor pressure in a closed system for a multicomponent mixture of solids knowing the initial water content for each component. From the final relative pressure and individual sorption-desorption isotherms, it is then possible to estimate the extent to which mixt. redistributes via the vapor phase among the various components.
Only few published studies are related to the permeability of hard gelatine capsules for water vapour. W. A. Strickland & al., J. Pharm. Sci., 51 (10) 1962, 1002–5 describes the water vapor diffusion through hard gelatin capsules and concludes that gelatine capsules offer little protection to a hygroscopic fill from atmospheric water vapour. To overcome this drawback in WO 97/04755 it has been suggested to incorporate polyol additives into the composition of the gelatin film of hard gelatin capsules.
It is well known that PVA film compositions have extremely low water vapour permeability, the lowest among known hydrosoluble film forming materials, and it is widely used for coating compositions, especially for pharmaceutical formulations like tablets as described in WO 96/01874.
EP-A-0 180 287 teaches the use of PVA in combination with cellulose ethers in hard capsule film compositions. In this compositions, the setting of the dipping solution is achieved by thermal gelation of a cellulose ether like Hydroxypropylmethyl cellulose (HPMC). However, to obtain acceptable setting properties of the film forming composition, the HPMC content must be very high, even higher than the PVA content. Consequently the benefits of the properties of PVA will significantly be reduced in such compositions.
The problem of the invention is therefore the provision of polyvinyl alcohol (PVA) compositions for the use in pharmaceutical, veterinary, food, cosmetic or other products like films for wrapping food, aspics or jellies, preferably for predosed formulations like soft or hard capsules and wherein the PVA composition has in aqueous solution sufficient setting ability.